sequential atra then il-2 for modulation of dendritic cells and treatment of metastatic renal cell cancer

Conditions: Kidney Cancer

Summary: rationale: tretinoin may help cells that are involved in the body's immune response to work better. interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. giving tretinoin together with interleukin-2 may kill more tumor cells. purpose: this randomized phase ii trial is studying how well giving three different doses of tretinoin together with interleukin-2 works in treating patients with stage iv kidney cancer.

objectives: primary * determine the ratio of dendritic cells (dc) to circulating immature cells (imc) before and after treatment with 3 different doses of tretinoin in patients with stage iv renal cell cancer. * assess in vitro immune response assays to tetanus toxoid and influenza virus peptide before and after treatment with tretinoin and interleukin-2 in these patients. secondary * determine the frequency of treatment-related side effects in these patients. * determine clinical objective response and progression-free survival of patients treated with this regimen. * correlate dc:imc ratio with clinical objective response in patients treated with this regimen. * correlate the extent of change of the dc:imc ratio with tretinoin dose and tretinoin blood levels in these patients. outline: this is a randomized, open-label study. specimens are stratified according to patient prognostic factors, tumor bulk, and extent of dendritic cell to circulating immature cell ratio derangement. patients are randomized to 1 of 3 tretinoin doses. patients are followed for up to 2 years. projected accrual: a total of 27-36 patients (9-12 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria:
disease characteristics: * histologically confirmed renal cell cancer * stage iv disease * histology with clear cell component * metastatic or incompletely resected disease * non-measurable disease allowed * underwent complete or partial nephrectomy more than 90 days ago * no unresected primary cancer * no more than 2 of the following adverse factors: * hemoglobin \< 10.0 g/dl * corrected calcium \> upper limit of normal (uln) * lactic dehydrogenase \> 1.5 times uln * eastern cooperative oncology group (ecog) performance status 2 * brain metastasis allowed provided more than 90 days of clinical and radiologic stability after the end of its active treatment patient characteristics: age * over 18 performance status * see disease characteristics * ecog 0-2 life expectancy * not specified hematopoietic * see disease characteristics hepatic * see disease characteristics * serum glutamic oxaloacetic transaminase (sgot) \< 3 times normal * bilirubin \< 2 times normal renal * see disease characteristics * creatinine clearance \> 40 ml/min cardiovascular * none of the following cardiovascular conditions within the past year: * uncontrolled hypertension * myocardial infarction * unstable angina * new york heart association class ii-iv congestive heart failure * serious cardiac arrhythmia requiring medication * class ii-iv peripheral vascular disease within the past year * other clinically significant cardiovascular disease immunologic * no history of immunodeficiency disease * no hiv infection * no ongoing serious infection other * not pregnant or nursing * negative pregnancy test * fertile patients must use two methods of effective contraception during and for 1 month (for women) or 6 months (for men) after study treatment * other prior malignancy allowed provided there is no evidence of active disease * no other medical contraindication to tretinoin or interleukin-2 * no serious non-healing wound, ulcer, or bone fracture prior concurrent therapy: biologic therapy * at least 60 days since prior immunotherapy chemotherapy * at least 60 days since prior cytotoxic chemotherapy endocrine therapy * see radiotherapy * no prior corticosteroids at \> physiologic replacement doses for \> 3 days within the past 90 days * concurrent tamoxifen, toremifene, megestrol, or gonadotropin-releasing hormone agonists allowed * concurrent inhaled steroids allowed radiotherapy * more than 7 days since prior external-beam radiotherapy * no steroid requirement during radiotherapy surgery * see disease characteristics * at least 30 days since other prior debulking surgery other * prior adjuvant therapy for resected, synchronous stage iv disease allowed * prior adjuvant therapy allowed * study therapy is not to be used as adjuvant therapy for completely resected late (\> 1 year until identification) solitary site of disease metastasis or non-metastatic disease * no prior participation in this clinical study * at least 60 days since other prior anticancer drugs * concurrent seizure medication allowed

Keywords: stage iv renal cell cancer recurrent renal cell cancer clear cell renal cell carcinoma